This program project application aims to continue studies on the molecular and biophysical mechanisms involved in neuronal signalling by the neurobiology group of the Biology Department at UCSD. Six separate projects, using a wide variety of animal models, from leeches and fruit flies to lobsters and frogs, will be undertaken. Ion channels, their regulation and modulation represent a major focus of the work since they represent identified membrane components of fundamental importance to neuronal signalling. Second messengers and intracellular cascade systems also represent a central unifying theme. Target selection during development and target mediated neuronal differentiation represent other foci of integrative signalling. The diversity of approaches provide an integrated analysis of signalling mechanisms from the molecular level to the functioning circuit.